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The Synthesis of Paracetamol from Benzene (Macroconcept Change)

OH

Paracetamol is both an analgesic and an antipyretic. Unlike aspirin and ibuprofen, paracetamol has no anti-inflammatory properties. Paracetamol is toxic to the liver and consequently high doses can be fatal:
CH3
Acute poisoning 10g in a single dose. Chronic poisoning 5g every 24 hours for a prolonged period of time.

C O

Paracetamol

The Synthesis of Paracetamol from Benzene (Macroconcept Change)


Step #1: Synthesis of Chlorobenzene from Benzene:
H H H C C C C H Benzene C C H H Cl

+
H

Cl Cl

AlCl3 H

C C

C C H

C C

+
H

H Cl

Chlorobenzene

The Synthesis of Paracetamol from Benzene (Macroconcept Change)


Step #2: Synthesis of Phenol from Chlorobenzene:
Cl H H C C C C H Chlorobenzene C C H H OH

+
H

NaOH

Reflux H

C C

C C H

C C

+
H

NaCl

Phenol

The Synthesis of Paracetamol from Benzene (Macroconcept Change)


Step #3: Nitration of Phenol:
OH H H C C C C C C H H2SO4 / HNO3 H H H C C OH C C C C H H

H Phenol

NO2 4-Nitrophenol

The Synthesis of Paracetamol from Benzene (Macroconcept Change)


Step #4: Reduction of the Nitro Group to an Amine:
OH H H C C C C C C H Sn / HCl H H H C C OH C C N C C H H

NO2 4-Nitrophenol

H H 4-Aminophenol

The Synthesis of Paracetamol from Benzene (Macroconcept Change)


Step #5: Synthesis of the Amide:
OH H H C C C C C C H O OH H C C H C C N C C C H H CH3

+
H

H3C C Cl

H Cl

N H H 4-Aminophenol

O Paracetamol

The Synthesis of Paracetamol from Benzene (Macroconcept Change)

Question:

If each step in the synthesis of paracetamol gives a yield of 80%, what mass of paracetamol will be synthesised from 1.0 kg of benzene?

The Synthesis of Ibuprofen from Benzene (Macroconcept Change)


CH3 CH3

H3C

C O

OH

Ibuprofen is classified as a non-steroidal anti-inflammatory drug (abbreviated to NSAID). Ibuprofen is mostly used to treat pain resulting from inflammation, e.g. rheumatism. The side-effects of ibuprofen are far less significant than those of other NSAID compounds such as aspirin.

Ibuprofen

The Synthesis of Ibuprofen from Benzene


Step #1: Friedel-Crafts alkylation:

H H H C C C C H C C H

+
H

H H H H C H H C C C Cl H H H

H H H H C C C H H H C H H AlCl3 H H C C C C H C C H H

H Cl

The Synthesis of Ibuprofen from Benzene


Step #2: Friedel-Crafts acylation:
H H H H C C C H H H C H H H O AlCl3 Cl H H H H

H H H H C C C H H H C H H H H C C C C H C C H H

H C C H

C C C H

C C C

C C O

+
H

H Cl

The Synthesis of Ibuprofen from Benzene


Step #3: Reduction of the ketone to an alcohol:
H H H H H C C C H H H C H H H NaBH4 H C C C C C H C C H H

H H H C C C H H H C H H H H H H C C C H C C C C C O H H

H C OH H H

The Synthesis of Ibuprofen from Benzene


Step #4: Substitution of OH by Br:
H H H H C C C H H H C H H H H C C C C C H C C H PBr3 H H H H H H C C C H H H C H H H C C C C C H C C H H

H C OH H H

H C Br H H

The Synthesis of Ibuprofen from Benzene


Step #5: Substitution of Br by CN:
H H H H C C C H H H C H H H H C C C C C H C C H H H H H C C C H H H C H H H

+
H

KC N H

C C

C C C H

C C

+
H

KBr

H C Br H H

H C C N H H

The Synthesis of Ibuprofen from Benzene


Step #6: Hydrolysis of CN to form COOH:
H H H H C C C H H H C H H H H C C C C C H C C H H / H2O H H
+

H H H H C C C H H H C H H H C C C C C H C C H H

H C C N H H

H C COOH H H

Ibuprofen

The Synthesis of Ibuprofen from Benzene


Question: The United Kingdom market for ibuprofen is 3 000 000 kg per year. a) If a typical ibuprofen tablet contains 0.2g of the drug, how many ibuprofen tablets are produced each year in the United Kingdom? b) The population of the United Kingdom is 60 000 000. i) How many ibuprofen tablets does a single person consume in the United Kingdom each year? ii) Evaluate how reasonable your answer is.